Prevalence of HIV-1 integrase mutations related to resistance to dolutegravir in raltegravir naive and pretreated patients.
PMID: 22716970
2012
Clinical microbiology and infection
Abstract: RTG-selected double and triple mutants, mostly the G140S/Q148H variant, were detected in only 32 (26.7%) RTG-treated patients.
The activity of the integrase inhibitor dolutegravir against HIV-1 variants isolated from raltegravir-treated adults.
PMID: 22878423
2012
Journal of acquired immune deficiency syndromes (1999)
Abstract: The median fold change to dolutegravir for isolates containing changes at G140S + Q148H, G140S + Q148R, T97A + Y143R, and N155H (thus including raltegravir signature resistance codons) were 3.75, 13.3, 1.05, and 1.37, respectively.
Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens.
Result: Dose-response profiles for variants T97A, G140S and Q148H were similar to those obtained in parallel with wild-type ROD9 (Figure S1), resulting in mean EC50 values that were not significantly different from the parental strain (Figure 2A).
Result: In contrast, the Y143C, N155H, and Q148H, K, and R changes each conferred statistically-significant declines in infectious virus production, with mean titers 3-15-fold lower than t
Figure: With the exception of Q148H versus raltegravir and Y143C versus elvitegravir, EC50 values for all strains shown in color were statistically greater than the corresponding values for wild-type ROD9 (P>0.05, ANOVA of log10-transformed EC50 values with Tukey's post-test).
"Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 ""deep"" sequencing."
Abstract: In the final paired samples that were tested while the subjects were on a raltegravir-containing regimen, DRM prevalence reached 100% in plasma but remained 1% in PBMC on day 177 post-therapy in Subject 3180 (
Result: For example, in Subject 3180 on day 177 post-therapy, 77% of the plasma virus shared identical sequences and contained the G140S/Q148H mutations (Figure 2A, day 177 white shading), but the same sequence could only be found in 1% of the counterpart PBMC population.
Result: In contrast, prevalence of plasma DRMs increased rapidly to 69% (Q148H and G140S) 54 days post-therapy.
Result: Note, however, that in subject 3180, the prevalence of Q148H and G140S in PBMC increased from 1% to 6% while the plasma prevalence decreased from 100% to 69%.
Monitoring the emergence of resistance mutations in patients infected with HIV-1 under salvage therapy with raltegravir in Rio de Janeiro, Brazil: a follow-up study.
Abstract: Among 12 (26.1%) raltegravir treated patients treatment failure was observed; major InI drug resistance mutations (G140S, Q148H and N155H, V151I, E92EQ, V151I, G163R) were noted in four of these cases (8.3% of the total InI-treated patients).
Result: Development of drug resistance mutations followed two patterns: major N155H with or without subsequent accessory V151I, E92EQ, V151I, G163R mutants (three cases) and Q148H accompanied by PMID: 20946407
2011
Clinical microbiology and infection
Abstract: Major mutation sites in the integrase (E92Q, F121Y, G140A/S, Y143C/R, Q148H/R/K and N155H) were not detected, and only a few minor mutation sites (L74M, V151I, E157Q, V165I, I203M, S230N and D232N) were identified in 21 strains (28%).
Cross-resistance profile determination of two second-generation HIV-1 integrase inhibitors using a panel of recombinant viruses derived from raltegravir-treated clinical isolates.
PMID: 20956600
2011
Antimicrobial agents and chemotherapy
Abstract: Samples with Q148H/R mutations had elevated fold change values with all compounds tested.
In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor.
PMID: 21115794
2011
Antimicrobial agents and chemotherapy
Abstract: S/GSK1349572 demonstrated activity against site-directed molecular clones containing the raltegravir-resistant signature mutations Y143R, Q148K, N155H, and G140S/Q148H (FCs, 1.4, 1.1, 1.2, and 2.6, respectively), while these mutants led to a high FC in the EC(50) of raltegravir (11- to >130-fold).
HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex.
Result: RAL resistance primarily occurs through several independent pathways containing mutations in IN (N155H and Q148H/K/R), with secondary mutations generally producing larger reductions in RAL susceptibility.
HIV mutation literature information.
PMID: 
2012
Clinical microbiology and infection
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